Process for recovering optical isomers and solvent, process for using solvent by circulation and process for reusing optical isomers in optical resolution

ABSTRACT

A process for recovering and reusing a solvent and optical isomers, characterized by using a simulated moving packed bed which comprises an inlet for an eluent, an outlet for an extract containing an optical isomer strongly adsorbable on the packing, an inlet for a liquid containing an optical isomer mixture and an outlet for a raffinate containing an optical isomer weakly adsorbable on the packing in this order in a packed bed column containing packings for optical resolution and arranged in a solvent circulation passage, and in which the inlets and the outlets are intermittently and successively moved in the direction of liquid flow in the packed bed; recovering the solvent and the optical isomer(s) from the resultant extract and/or raffinate; returning the recovered solvent into the solvent circulation passage; or when the solvent is not recovered, heating the extract or raffinate to racemize an undesired optical isomer and reusing the resultant solution containing a racemic modification for the separation of the optical isomers with the simulated moving bed system.

FIELD OF INDUSTRIAL APPLICATION

The present invention relates to a process for recovering opticalisomers and a solvent, a process for using the solvent by circulationand a process for reusing the optical isomers. In particular, thepresent invention relates to a process for recovering optical isomersand a solvent, wherein the optical isomers can be efficiently separatedfrom each other and the solvent used for the optical resolution can beefficiently recovered, a process for using the solvent by circulation,wherein the solvent recovered by the recovering process of the presentinvention is reused for the effective utilization of the solvent, and aprocess for reusing the optical isomers, wherein the intended opticalisomers obtained by the optical resolution are reused without beingdiscarded so as to further improve the efficiency of the opticalresolution.

PRIOR ART

It is well known that optical isomers have different effects on theliving body, though they are chemically the same. Therefore, it is anextremely important problem in the industrial fields of medicines,pharmacy, biochemistry, etc., to prepare an optically pure compound inorder to improve the efficacy of the medicine per unit quantity and toprevent drug-induced sufferings caused by adverse reactions of the drug.For the separation of such an optical isomer mixture, i.e., opticalresolution of them, a diastereomer method, crystallization method,enzyme method, separating membrane method or the like has been employedheretofore. However, such a method is generally unsuitable, since thekinds of the compounds which can be optically resolved are usuallylimited. Although chromatography can be employed for the opticalresolution, the chromatographic methods known at present are of a batchtype and hence cannot avoid discontinuous and unstationary operations,which is unsuitable for the mass processing. Further, thischromatographic method has another defect in that since a large amountof an eluent is necessitated and the concentration of the intendedcompound in the eluate is low, much energy and complicated steps arenecessitated for the recovery.

An object of the present invention is to provide a novel process whichcan separate optical isomers and a solvent efficiently from a largeamount of a mixture comprising the optical isomers. Another object ofthe present invention is to provide a process for efficiently separatingeach of optical isomers and a solvent from a large amount of a mixturecomprising the optical isomers and also reusing the recovered solvent.

DISCLOSURE OF THE INVENTION

The invention which solves the above problem relates to a process forrecovering optical isomers and a solvent in optical resolution byintroducing a liquid containing an optical isomer mixture and an eluentinto a packed bed containing packings for optical resolution, havingboth ends connected to each other through a fluid passage to be endlessand circulating the liquids therein by one-way flow, and simultaneouslyrecovering a liquid containing one optical isomer and a liquidcontaining the other optical isomer which are separated from the packedbed, characterized by arranging an inlet for the eluent, an outlet for aliquid (extract) containing an easily adsorbable optical isomer, aninlet for the liquid containing an optical isomer mixture, and an outletfor a liquid (raffinate) containing a difficulty adsorbable opticalisomer in this order in the direction of liquid flow onto the packedbed, and recovering the solvent and optical isomers from the extractand/or raffinate thus obtained with a simulated moving bed system suchthat the inlets and the outlets are intermittently and successivelymoved in the direction of liquid flow in the bed.

Further, the invention relates to the above mentioned process forrecovering optical isomers and a solvent, wherein the packing foroptical resolution has a particle diameter of 1 to 100 μm,

the invention relates to the above mentioned process for recoveringoptical isomers and a solvent in optical resolution, wherein the solventis separated from the extract and/or raffinate obtained with thesimulated moving bed system with an evaporator and/or a still,

the invention relates to the above mentioned process for recoveringoptical isomers and a solvent in optical resolution, wherein the aboveevaporator and/or still is of a reduced pressure type,

the invention relates to a process for using a solvent by circulation,characterized by returning the solvent recovered by the above mentionedprocess into the fluid passage,

the invention relates to the above mentioned process for using a solventby circulation, wherein the recovered solvent has a purity of at least98% and,

the invention relates to a process for reusing an optical isomer,wherein the optical isomer as an antipode in the above mentioned extractor raffinate is racemized and the resultant liquid containing an opticalisomer mixture is returned into an inlet for a liquid containing anoptical isomer mixture.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a drawing for illustrating one example of the apparatusesusable for conducting the process of the present invention.

FIG. 2 is a drawing for illustrating another example of the apparatusesusable for conducting the process of the present invention.

1 to 12: unit packed up

13: line for feeding eluent

14: line for ejecting extract

15: line for feeding liquid containing optical isomer mixture

16: line for ejecting raffinate

17: recycle line

18: circulation pump

19: first falling film evaporator

20: second falling film evaporator

21: forced film evaporator

22: recovery tank

23: reservoir

24: racemization tank

25: still

The present invention will be described in detail in the following.

A. Simulated moving bed:

In the simulated moving bed system, use is made of, for example, asimulated moving bed as shown in FIG. 1 which is divided into aplurality of (for example, 12 or 8) unit packed beds arranged in seriesin the liquid passage in which liquid is circulated. The liquid isunidirectionally circulated in the liquid passage. The number of theunit packed beds in the simulated moving bed is not limited to thosedescribed above, but can be suitably selected depending on the scale andfrom the viewpoint of reaction engineering.

The simulated moving bed has an inlet for an eluent, an outlet forejecting a liquid (extract) containing an optical isomer stronglyadsorbable on the packing, an inlet for a liquid containing an opticalisomer mixture, and an outlet for ejecting a liquid (raffinate)containing an optical isomer weakly adsorbable on the packing in thisorder in the direction of liquid flow, and they can be intermittentlyand successively moved in the direction of liquid flow in the packedbed.

The simulated moving bed system per se is well known as described in,for example, Japanese Patent Publication-B No. 15681/1967. However, thesimulated moving bed system has heretofore been employed only for theproduction of fructose, separation of maltose and recovery of co-enzymesand no process has been described at all for separating optical isomersby this system.

In the simulated moving bed system shown in FIG. 1, an inlet for aneluent, an outlet for an extract, an inlet for a liquid containing anoptical isomer mixture and an outlet for a raffinate are provided forevery three unit packed beds. These inlets and outlets areintermittently and successively moved by means of, for example, rotaryvalves.

Kind of packings for optical resolution and the like

Each unit packed bed contains packings having an optical resolvingability. The packings include those for optical resolution made of anoptically active polymeric compound and a low-molecular compound havingan optical resolving ability. Examples of the optically active polymericcompounds include polysaccharide derivatives (such as esters andcarbamates of cellulose and amylose), polyacrylate derivatives, packingscomprising a polyamide derivative carried by silica gel, and packingsprepared by granulating the polymer per se without using any silica gel.Examples of the low-molecular compounds having an optical resolvingability include crown ethers and derivatives thereof and cyclodextrinand derivatives thereof. These low-molecular compounds are usuallyemployed by being supported on a support such as silica gel.

Commercially available packings for optical resolution are also usable.Examples of preferred ones include CHIRALCEL OB (registered trade name),CHIRALCEL OD (registered trade name), CROWNPAK CR(+) (registered tradename), CHIRALCEL CA-1 (registered trade name), CHIRALCEL OA (registeredtrade name), CHIRALCEL OB (registered trade name), CHIRALCEL OK(registered trade name), CHIRALCEL OJ (registered trade name), CHIRALCELOC (registered trade name), CHIRALCEL OF (registered trade name),CHIRALCEL OG (registered trade name), CHIRALPAK WH (registered tradename), CHIRALPAK WM (registered trade name), CHIRALPAK WE (registeredtrade name), CHIRALPAK OT(+) (registered trade name), CHIRALPAK OP(+)(registered trade name), CHIRALPAK AS (registered trade name) andCHIRALPAK AD (registered trade name) all of which are products of DaicelChemical Industries, Ltd.

Particle diameter of packing

Although the average particle diameter of the packing varies dependingon the kind of the optical isomers to be resolved, the volume flow rateof the solvent flowing in the simulated moving bed, etc., it is usually1 to 100 μm, preferably 5 to 75 μm. In order to keep the pressure dropin the simulated moving bed on a low level, it is desirable to regulatethe average particle diameter of the packing to 15 to 75 μm. When theaverage particle diameter of the packing is within the above-describedrange, the pressure drop in the simulated moving bed can be reduced to,for example, 10 kgf/cm² or below. On the contrary, as the averageparticle diameter of the packing increases, the number of thetheoretical adsorption plates decreases. Therefore when only the numberof the practical theoretical adsorption plates is to be attained, theaverage particle diameter of the above-described packing is usually 1 to50 μm.

Eluent

The eluents to be fed through the inlet for an eluent include, forexample, organic solvents such as alcohols, e.g. methanol, ethanol andisopropanol, hydrocarbons, e.g. hexane, and aqueous salt solutions suchas aqueous copper sulfate solution and aqueous perchlorate solution. Theeluent is suitably selected depending on the kind of the compounds to beoptically resolved.

Optical isomer to be optically resolved

The optical isomer mixture to be fed through an inlet for a liquidcontaining an optical isomer mixture is not particularly limited. Theoptical isomer mixture may comprise various compounds used in the fieldsof medicines, agricultural chemicals, foods, feeds, flavors, etc., suchas thalidomide (a medicine), EPN (an organophosphorus agriculturalchemical), monosodium glutamate (a chemical seasoning) and menthol (aflavor), and also optically active alcohols and optically active esters.

Steps in the simulated moving bed system

The separation of optical isomers by adsorption with the simulatedmoving bed system of the present invention is conducted by thecontinuous circulation of the basic steps including those of adsorption,concentration, desorption and recovery of the eluent, which will bedescribed below.

(1) Adsorption step:

When an optical isomer mixture is brought into contact with packings, anoptical isomer (strongly adsorbable component) easily adsorbable on thepacking is adsorbed and the other optical isomer (weakly adsorbablecomponent) difficulty adsorbable on the packing is recovered as theraffinate together with the eluent.

(2) Concentration step:

The packing having the strongly adsorbable component adsorbed thereon isbrought into contact with a part of an extract which will be describedbelow to expel the weakly adsorbable component remaining on the packing,thereby concentrating the strongly adsorbable component.

(3) Desorption step:

The packing containing the strongly adsorbable component thusconcentrated is then brought into contact with the eluent to expel thiscomponent from the packing to discharge it as the extractor togetherwith the eluent from the simulated moving bed.

(4) Eluent-recovering step:

The packing on which substantially only the eluent is adsorbed is thenbrought into contact with a part of the raffinate, whereby a part of theeluent contained in the packing is recovered as an eluent recovery.

The present invention which will be described in more detail withreference to the attached drawings is as follows.

In FIG. 1, numerals 1 to 12 refer unit packed beds containing packings,and they are connected to each other through a liquid passage. Numeral13 refers to an eluent-feeding line, 14 to an extract ejecting line, 15to a line for feeding a liquid containing an optical isomer mixture, 16to a raffinate ejecting line, 17 to a recycle line and 18 to acirculation pump.

In the arrangement of the unit packed beds 1 to 12 and lines 13 to 16shown in FIG. 1, the unit packed beds 1 to 3 take part in the desorptionstep, the unit packed beds 4 to 6 in the concentration step, the unitpacked beds 7 to 9 in the adsorption step, and the unit packed beds 10to 12 in the eluent-recovering step.

In this simulated-moving bed, the eluent-feeding line, the line forfeeding a liquid containing an optical isomer mixture and the respectiveejecting lines are moved at a distance corresponding to one unit packedbed in the direction of solvent flow by, for example, operating valvesat predetermined time intervals.

Accordingly, in the second stage, the unit packed beds 2 to 4 take partin the desorption step, the unit packed beds 5 to 7 in the concentrationstep, the unit packed ones 8 to 10 in the adsorption step and the unitpacked ones 11 to 1 in the eluent-recovering step. By successivelyconducting such an operation, the respective steps move at a distancecorresponding to one unit packed bed, and the separation treatment ofthe optical isomer mixture is conducted continuously and efficiently.

The extract thus ejected with the simulated moving bed system comprisesan optical isomer having an optical purity of as high as at least 90%,for example, at least 95% or even at least 98%, contained in thesolvent, and the raffinate comprises the other optical isomer having anoptical purity of as high as that described above in the solvent.

Another embodiment of the simulated moving bed

The simulated moving bed to be used in the process of the presentinvention is not limited to that shown in FIG. 1 but another simulatedmoving bed shown in FIG. 2 is also usable.

In the arrangement of unit packed beds 1 to 8 and lines 13 to 16 shownin FIG. 2, the unit packed bed 1 takes part in the elution andrecovering steps, the unit packed beds 2 to 5 in the adsorption step,the unit packed beds 6 and 7 in the concentration step, and the unitpacked bed 8 in the desorption step.

In such a simulated moving bed, the liquid-feeding lines and ejectinglines are moved at a distance corresponding to one unit packed bed inthe direction of liquid flow by, for example, operating valves atpredetermined time intervals. Accordingly, in the next arrangement ofthe unit packed beds, the unit packed bed 2 takes part in eluent-feedingstep, the unit packed beds 3 to 6 in the adsorption step, the unitpacked beds 7 and 8 in the concentration step, and the unit packed bed 1in the desorption step. By successively conducting such an operation,the separation treatment of the optical isomer mixture is conductedcontinuously and efficiently.

B. Recovery of the solvent:

In the present invention, one or both of the extract and raffinateobtained according to the above-described simulated moving bed systemare sent to the solvent-recovering step.

The recovery of the solvent and separation of the optical isomers fromthe extract and/or raffinate can be conducted in an evaporator and/or astill. The evaporator and the still are preferably of a reduced pressuretype. The evaporator of a reduced pressure type is preferred, since theoptical isomers can be separated without denaturalizing them by heating,since oxidation can be prevented and the evaporation temperature can belowered.

The evaporators usable herein are preferably film evaporators such as aforced film evaporator, ascending film evaporator, falling filmevaporator, or stirred liquid film evaporator. These evaporators areusable either singly or in combination of two or more evaporators of thesame or different types. The stills are preferably molecular stills suchas a batchwise molecular still, falling film molecular still orcentrifugal film molecular still. These molecular stills of a reducedpressure type are usable either singly or in combination of two or morestills of the same or different types.

In the process of the present invention, it is preferred that theextract and/or raffinate ejected from the simulated moving bed isseparated in a separator comprising a combination of two or three kindsof falling film evaporator and forced film evaporator, since the use ofthe combination of the two or three apparatuses can reduce the residencetime in these apparatuses, thereby preventing the racemizationadvantageously. A combination of two or more apparatuses of the samekind arranged in series or a combination of them with the molecularstill is also desirable.

Specifically, as shown in FIG. 1, the extract is concentrated to about30 to 50% in the first falling film evaporator 19, then to about 40 to70% in the second falling film evaporator 20, and further to about 60 to99% in a forced film evaporator 21.

The solvent recovered in the evaporator is usually stored in a recoverytank temporarily. In FIG. 1, numeral 22 refers to a recovery tank fortemporarily storing recovered solvent. The concentrate containing anoptical isomer obtained by the concentration with the evaporator istemporarily stored in a reservoir. Numeral 23 in FIG. 1 refers to thereservoir.

On the other hand, the raffinate contains another optical isomer, whichis an antipode of the optical isomer contained in the extract, and thesolvent. The recovery of the solvent from the raffinate can be conductedin the same manner as that of the recovery of the solvent from theextract.

C. Reuse of the solvent:

In the process of the present invention, the solvent recovered asdescribed above is recycled for use as the eluent or reused for thepreparation of a liquid containing an optical isomer mixture. In such acase, the purity of the solvent to be reused is at least 98%. Forobtaining such a purity, the use of a still is preferable. In FIG. 1,the concentration of the solvent stored in the recovery tank 22 isincreased to a necessary purity in a still 25. When the above purity canbe kept, the separation of the optical isomers can be efficientlyconducted by the simulated moving bed system.

D. Reuse of the optical isomers:

In the process of the present invention, it is also preferred to convertan optical isomer which is not an intended antipode contained in theextract or raffinate into the racemic modification by heating and thento return the solvent containing the racemic modification into the linefor feeding a liquid containing an optical isomer mixture after, ifnecessary, adjusting the concentration of the liquid. In this case, theextract or raffinate can be directly racemized, or the racemization canbe conducted by treating a solution containing an optical isomerobtained after recovering the solvent from the extract or raffinate, orthe racemic modification thus obtained can be dissolved in a freshsolvent to obtain a solution containing the racemic modification. Theracemization of the optical isomer can be conducted by heating or byusing an enzyme. In either case, well-known racemization methods can besuitably selected. Irrespective of the employed racemization method, theracemization conditions are suitably determined depending on the kind ofthe optical isomer.

In FIG. 1, the raffinate is heated in a racemization tank 24 and thesolvent containing the racemic modification thus obtained is returnedinto a line 15 for feeding a liquid containing an optical isomermixture.

By thus separating a desired optical isomer as, for example, the extractand, on the other hand, heating the raffinate containing an undesiredoptical isomer to form a racemic modification to be reused, an intendedoptical isomer can be separated more efficiently. Although the intendedoptical isomer is contained in the extract in the above description ofthe present invention given with reference to the drawings, the intendedoptical isomer may be contained in the raffinate in another case. In thelatter case, the term "extract" in the above description referring tothe extract is to be replaced by "raffinate", so that the matter can beeasily understood.

According to the present invention, an optical isomer mixture can becontinuously and efficiently separated and the solvent can be recoveredafter use. Since the recovered solvent can be reused as the solventcirculating through the simulated moving bed, the solvent is not wastedand the amount of eluent used is small, so that a closed system having ahigh efficiency with respect to the solvent can be obtained. Further,the adsorption efficiency is improved by regulating the average particlediameter of the packing for optical resolution to be packed in thesimulated moving bed to 1 to 100 μm. In addition, by racemizing theoptical isomer which is an antipode contained in the raffinate orextract separated in the simulated moving bed system, the raffinate orextract can convert a solution containing a racemic modification. Andsince the solution is reused as a liquid containing an optical isomermixture to be fed, the intended optical isomer can be separated in ahigh yield.

EXAMPLES

The following Examples will further illustrate the present invention,which by no means limit the present invention.

EXAMPLE 1

A simulated moving bed apparatus shown in FIG. 1, which was prepared byconnecting twelve columns having an inner diameter of 2 cm and a lengthof 50 cm as the unit packed beds to each other and filling them withpackings for optical isomer resolution (CHIRALCEL OB having a particlediameter of 20 μm; a product of Daicel Chemical Industries, Ltd.), wasused. In this simulated moving and apparatus were arranged the columnsso that every three unit packed beds took part in the adsorption step,concentration step, desorption step and eluent-recovering step. 6 ml/minof 1,3-butanediol diacetate (total isomer concentration: 1,000 mg/ml)was fed as a liquid containing an optical isomer mixture. 27.9 ml/min ofa liquid mixture of hexane and isopropanol (volume ratio: 9/1) was fedas the eluent. The solvent circulating the solvent circulation passagewas the same as the eluent.

26.6 ml/min of an extract containing a stongly adsorbable optical isomer(concentration: 103.7 mg/ml; optical purity: 98% e.e.) was obtainedthrough the outlet for the extract of the simulated moving bedapparatus.

On the other hand, 7.3 ml/min of a raffinate containing a weaklyadsorbable, other optical isomer (concentration: 411.4 mg/ml; opticalpurity: 98% e.e.) was obtained through the outlet for the raffinate ofthe simulated moving bed apparatus.

The extract obtained as described above was fed into the first fallingfilm evaporator at 70° C. under atmospheric pressure. The concentrateobtained in this evaporator was fed into the second falling filmevaporator at 43° C. under 50 Torr and then the concentrate obtained inthis second evaporator was fed into a forced film evaporator at 10° C.under 50 Torr to give a concentrate containing the strongly adsorbableoptical isomer in a concentration of at least 98% from the forced filmevaporator. The solvent recovered from the respective evaporators wasstored in the reservoir.

On the other hand, the raffinate obtained as described above was heatedat 90°0 C. for 5 hours to give a solution containing a racemicmodification.

The solvent stored in the reservoir was reused as the circulatingsolvent in the simulated moving bed apparatus, and the solutioncontaining the racemic modification in the heating tank was returnedinto the line for feeding a liquid containing an optical isomer mixture.

By the above process, the strongly adsorbable optical isomer having anoptical purity of 98% e.e. could be obtained in an amount of at least83% based on the racemic modification fed into this system.

COMPARATIVE EXAMPLE 1

The separation was conducted batchwise by using the same packing and thesame starting material as those in Example 1 and a single column tocompare the throughput and the utilization rate of the eluent. Theresults are given in Table 1.

                  TABLE 1                                                         ______________________________________                                                    Simulated moving                                                                         Batchwise                                                          bed process                                                                              process                                                ______________________________________                                        Throughput per                                                                              2.4          0.084                                              unit packing per                                                              unit time                                                                     (mg/ml-bed · min)                                                    Utilization rate                                                                            0.0093       2.0                                                of eluent                                                                     (mg/ml-feed)                                                                  ______________________________________                                    

It is apparent from this Table 1 that the employment of the simulatedmoving bed process is superior to that of the batchwise process in thethroughput and the utilization rate of the eluent.

EXAMPLE 2

The same apparatuses as those of Example 1 were used except that columnshaving an inner diameter of 3 cm and a length of 100 cm were used as theunit packed column and CHIRALCEL OB having an average particle diameterof 30 to 50 μm was used as the packing. 6 ml/min of α-phenylethyl alchol(total isomer concentration: 1,000 mg/ml) was fed. 61.4 ml/min of aliquid mixture of hexane and isopropanol (volume ratio: 9/1) was fed asthe eluent. The solvent circulating the solvent circulation passage wasthe same as the eluent.

58.5 ml/min of an extract containing a strongly adsorbable opticalisomer (concentration: 28.6 mg/ml; optical purity: 98% e.e.) wasobtained through the outlet for the extract of the simulated moving bedapparatus.

On the other hand, 8.9 ml/min of a raffinate containing a weaklyadsorbable, other optical isomer (concentration: 336 mg/ml; opticalpurity: 98% e.e.) was obtained through the outlet for the raffinate ofthe simulated moving bed apparatus.

The extract obtained as described above was treated in the same manneras that of Example 1 to give a concentrate containing the stronglyadsorbable optical isomer in a concentration of at least 98% by weight.The solvent recovered from the evaporator and the molecular still wasstored in the reservoir.

The solvent stored in the reservoir was reused as the circulatingsolvent in the simulated moving bed apparatus, and the raffinate wastreated in the same manner as that of Example 1. The resultant solutioncontaining a racemic modification was returned into the line for feedinga liquid containing an optical isomer mixture.

COMPARATIVE EXAMPLE 2

The separation was conducted batchwise by using the same packing and thesame starting material as those of Example 2 and a single column tocompare the throughput and the utilization rate of the eluent. Theresults are given in Table 2.

                  TABLE 2                                                         ______________________________________                                                    Simulated moving                                                                         Batchwise                                                          bed process                                                                              process                                                ______________________________________                                        Throughput per                                                                              0.53         0.014                                              unit packing per                                                              unit time                                                                     (mg/ml-bed · min)                                                    Utilization rate                                                                            0.02         4.5                                                of eluent                                                                     (mg/ml-feed)                                                                  ______________________________________                                    

EXAMPLE 3

A simulated moving bed apparatus shown in FIG. 2, which was prepared byconnecting eight columns having an inner diameter of 2 cm and a lengthof 15 cm as the unit packed beds to each other and filling them withpackings for optical isomer resolution (CHIRALCEL OB having a particlediameter of 45 μm; a product of Daicel Chemical Industries, Ltd.) wasused. 5.9 ml/min of a mixed solution containing 4,200 ppm of racemicmodification of α-phenylethyl alcohol was fed as a liquid containing anoptical isomer mixture in the simulated moving bed apparatus. 24.2ml/min of a liquid mixture of hexane and isopropanol (volume ratio:90/10) was fed as the eluent. The solvent circulating the solventcirculation passage was the same as the eluent. The liquid-feeding linesand ejecting lines were moved at a distance corresponding to one unitpacked bed in the direction of liquid flow by automatically switching aneight-way rotary valve at intervals of 3 min to continuously conduct thetreatment at 25° C. in a certain period of time.

20.2 ml/min of an extract containing a strongly adsorbable opticalisomer [(R)-(+)-α-phenylethyl alcohol](concentration: 613.4 ppm; opticalpurity: at least 99.9% e.e.) was obtained through the outlet for theextract of the simulated moving bed apparatus.

On the other hand, 9.7 ml/min of a raffinate containing a weaklyadsorbable, other optical isomer (concentration: 1,251.5 ppm; opticalpurity; at least 99.9% e.e.) was obtained through the outlet for theraffinate of the simulated moving bed apparatus.

The pressure drop in this simulated moving bed apparatus was 7.9 kg/cm².

The extract obtained as described above was fed into the same solventrecovering apparatuses as those of Example 1 to give a concentratecontaining the strongly adsorbable optical isomer in a concentration of98% by weight and solvent having a purity of at least 99% by weight. Therecovered solvent was stored in the reservoir.

The solvent stored in the reservoir was reused in the fluid passage inthe simulated moving bed apparatus, and the raffinate was converted intoa solution containing a racemic modification by heating and returnedinto the line for feeding a liquid containing an optical isomer mixture.

We claim:
 1. A process for recovering optical isomers and a solvent froma mixture containing the same comprising the steps of: introducing aliquid containing an optical isomer mixture and an eluent into a packedbed column containing packings for optical resolution, said columnhaving its ends connected to each other through a fluid passage so thatliquid may be circulated therethrough in endless, one-way flowrelationship, an inlet for the eluent, an outlet for a liquid extractcontaining a strongly adsorbable isomer mixture, an inlet for the liquidcontaining the optical isomer mixture and an outlet for a liquidraffinate containing a weakly adsorbable optical isomer arranged in thatorder in the liquid flow direction along the packed bed column;circulating said liquid containing the optical isomer mixture and eluentin one-way flow through the column; simultaneously recovering a liquidcontaining one optical isomer and a liquid containing another opticalisomer from the column; recovering the solvent and optical isomers fromthe extract and/or raffinate separated from the column; andintermittently and successively moving the inlets and outlets in thedirection of liquid flow along the column.
 2. The process for recoveringoptical isomers and a solvent according to claim 1, wherein the packingfor optical resolution has a particle diameter of 1 to 100 μm.
 3. Theprocess for recovering optical isomers and a solvent according to claim1, wherein the packing for optical resolution has a particle diameter of15 to 70 μm.
 4. A process for recovering optical isomers and a solventfrom a mixture containing the same comprising the steps of: introducinga liquid containing an optical isomer mixture and an eluent into apacked bed column containing packings for optical resolution, saidcolumn having its ends connected to each other through a fluid passageso that liquid may be circulated therethrough in endless, one-way flowrelationship, an inlet for the eluent, an outlet for a liquid extractcontaining a strongly adsorbable isomer mixture, an inlet for the liquidcontaining the optical isomer mixture and an outlet for a liquidraffinate containing a weakly adsorbable optical isomer arranged in thatorder in the liquid flow direction along the packed bed column;circulating said liquid containing the optical isomer mixture and eluentin one-way flow through the column; simultaneously recovering a liquidcontaining one optical isomer and a liquid containing another opticalisomer from the column; recovering the optical isomers from the extractand/or raffinate separated from the column; separating the solvent fromthe extract and/or raffinate with an evaporator and/or a still; andintermittently and successively moving the inlets and outlets in thedirection of liquid flow along the column.
 5. The process for recoveringoptical isomers and a solvent according to claim 4, wherein theevaporator and/or still is of a reduced pressure type.
 6. A process forrecovering optical isomers and a solvent from a mixture containing thesame comprising the steps of: introducing a liquid containing an opticalisomer mixture and an eluent into a packed bed column containingpackings for optical resolution, said column having its ends connectedto each other through a fluid passage so that liquid may be circulatedtherethrough in endless, one-way flow relationship, an inlet for theeluent, an outlet for a liquid extract containing a strongly adsorbableisomer mixture, an inlet for the liquid containing the optical isomermixture and an outlet for a liquid raffinate containing a weaklyadsorbable optical isomer arranged in that order in the liquid flowdirection along the packed bed column; circulating said liquidcontaining the optical isomer mixture and eluent in one-way flow throughthe column; simultaneously recovering a liquid containing one opticalisomer and a liquid containing another optical isomer from the column;recovering the solvent and optical isomers from the extract and/orraffinate separated from the column; returning the recovered solventinto the fluid passage; and intermittently and successively moving theinlets and outlets in the direction of liquid flow along the column. 7.The process for recovering optical isomers and a solvent according toclaim 6, wherein the recovered solvent has a purity of at least 98%.